Equine regenerative medicine: yay or neigh?

Horses have long been admired for their beauty, spirit, strength and speed. While a dog might be man’s best friend, the horse has been a near essential companion on humankind’s journey through history. While fewer horses are kept as a sole means of transport these days, they remain a big part of our lives, not least on the race track, where thousands of people still gather to watch them compete. What’s perhaps less well-known, however, is that the horse has also come to the fore as a model for regenerative medicine.

Despite limited understanding of their effects in vivo, stem cells are widely used in veterinary medicine, particularly in racehorses. Successful racehorses can be worth huge amounts of money – British racehorse Frankel has been valued at £100 million. With such prizes at stake, when a horse suffers an injury which prevents them from training and racing, any treatment which might help them reach or return to their winning ways will be considered and perhaps demanded by the owners and trainers involved.

Most commonly, stem cells are used to treat damaged tendons and ligaments in the horses legs; such injuries are slow to heal and often result in scar tissue which leaves the horse prone to further injury. Studies have shown that treatment with stem cells can result in better repair, and reduce the chance of another injury, although rehabilitation remains a slow process. Stem cells have also been used in degenerative joint disease (such as osteoarthritis) and in laminitis – an extremely painful condition affecting the hooves.

Two recently published research articles in Stem Cell Research & Therapy have both investigated this area, looking at the use of equine mesenchymal stromal cells (MSCs – a type of stem cell which is multipotent).

Originally found in bone marrow, MSCs have since been isolated from other sources. In their article, Van de Walle and colleagues have compared equine MSCs from three less-invasive sources: peripheral blood, umbilical cord blood and the umbilical cord matrix (also known as Wharton’s jelly, this gelatinous substance supports and protects the umbilical cord blood vessels).

One use of these MSCs is for allogeneic therapy, where cells from one donor are used to treat a different recipient – as in most human blood transfusions. This compares to autologous therapy, where the cells used for the treatment are cultured from samples donated by the same individual.

Where time is of the essence in starting treatment the advantage of allogeneic therapy – using cells which have been previously donated, cultured and stored – is obvious, as it can take weeks to culture autologous cells from the affected individual. However, with allogeneic therapy the cells will not be genetically identical, so there may be an increased risk of an immune response.

This immune response is linked to proteins of the major histocompatibility complex (MHC), which span the cell membrane and allow recognition of cells as “self” or “other”. Fortier and colleagues demonstrated that some equine bone marrow-derived MSCs express these proteins and some don’t. What’s more, those that do were found to be capable of inciting an immune response in vitro.

So what does this research mean, given that MSCs are already being used in equine veterinary medicine?

Fortier and colleagues have made a strong case that all potential donor MSCs should be screened for MHC protein expression before being used in allogeneic therapy.

They’ve also suggested that “it is not safe to assume that donor MSCs from any breed of horse can be used in a recipient horse of the same breed without the potential for an immune reaction.” So if you do happen to own a share in a racehorse with a blown tendon, it’s worth asking a bit more about the origin of any proposed cell therapies!

Meanwhile Van de Walle and colleagues’ results offer hope that umbilical cord blood could be a promising, less-invasive source of MSCs for equine regenerative therapies, with potential for allogeneic applications; although further insight is needed into whether they will incite an immune response.

For the rest of us, these results are important because the horse is one of the best models we have for assessing regenerative therapies for musculoskeletal disorders – sporting injuries or degenerative disorders – such as tendonitis, cartilage damage and osteoarthritis. The more we understand about MSC therapy in horses, the greater chance we have for successful translation into humans.

For more information about stem cells in veterinary medicine, see this review from Lisa Fortier and Alexander Travis.